A Combined Proteomics and Metabolomics Profiling of Gastric Cardia Cancer Reveals Characteristic Dysregulations in Glucose Metabolism
A Combined Proteomics and Metabolomics Profiling of Gastric Cardia Cancer Reveals Characteristic Dysregulations in Glucose Metabolism
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胃癌的蛋白质组学和代谢组学联合分析揭示了葡萄糖代谢的特征性失调
DOI：
10.1074/mcp.m110.000661
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发表时间：
2010-12-01
影响因子：
7
通讯作者：
Xie, Dong
中科院分区：
文献类型：
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作者：
Cai, Zhen;Zhao, Jiang-Sha;Xie, Dong
贲门癌是发生在胃食管交界处的恶性肿瘤之一。尽管其死亡率和发病率高，但其发生和发展的分子机制在很大程度上是未知的。在这项研究中，使用蛋白质组学和代谢组学方法，我们发现，参与葡萄糖代谢的几种酶及其相关代谢中间产物的水平在GCC中失调。在这些酶中，控制乳酸流出的两个亚基，乳酸脱氢酶A（LDHA）和丙酮酸脱氢酶B（PDHB），在体外进行了进一步分析。AGS胃癌细胞中LDH亚基LDHA的下调或PDH亚基PDHB的过表达均能使甘草酸进入Krebs循环而非糖酵解过程，从而抑制细胞生长和迁移。我们的研究结果反映了一个重要的葡萄糖代谢特征，特别是在GCC的发展中，葡萄糖酸流出的失调。从糖酵解到克雷布斯循环的强制转换对GCC进展具有抑制作用，为这种疾病提供了潜在的治疗靶点。Molecular & Cellular Proteomics 9：2617-2628，2010.
Gastric cardia cancer (GCC), which occurs at the gastric-esophageal boundary, is one of the most malignant tumors. Despite its high mortality and morbidity, the molecular mechanism of initiation and progression of this disease is largely unknown. In this study, using proteomics and metabolomics approaches, we found that the level of several enzymes and their related metabolic intermediates involved in glucose metabolism were deregulated in GCC. Among these enzymes, two subunits controlling pyruvic acid efflux, lactate dehydrogenase A (LDHA) and pyruvate dehydrogenase B (PDHB), were further analyzed in vitro. Either down-regulation of LDH subunit LDHA or overexpression of PDH subunit PDHB could force pyruvic acid into the Krebs cycle rather than the glycolysis process in AGS gastric cancer cells, which inhibited cell growth and cell migration. Our results reflect an important glucose metabolic signature, especially the dysregulation of pyruvic acid efflux in the development of GCC. Forced transition from glycolysis to the Krebs cycle had an inhibitory effect on GCC progression, providing potential therapeutic targets for this disease. Molecular & Cellular Proteomics 9: 2617-2628, 2010.